The ability to sense and discriminate a large collection of chemical and visual clues is central for several behaviors of insects that are vectors for pathogens responsible for many important human diseases. In particular, olfaction plays a major role in host seeking and selection behavior of blood-feeding female mosquitoes (Diptera: Culicidae) and as such, constitutes a critical component of the mosquito's ability to transmit diseases such as malaria and dengue. Furthermore, the strong preference for human hosts (anthropophily) exhibited by the principal African malaria vector mosquito Anopheles gambiae s.s. forms a large part of the basis for its inherent ability to transmit human malaria. In as much as an understanding of these chemosensory mechanisms and their underlying chemical cues may be useful in the development of anti-malarial control strategies targeted against Anopheline disease vectors, a molecular characterization in these mosquitoes has been initiated. The objectives of this study focus on an examination of the molecular genetics of anthropophily and consist of the isolation and characterization of genes that make up the peripheral components of the olfactory apparatus in An. gambiae and An. quadriannulatus. We hypothesize that these genes encoding odorant binding proteins (OBPs), odorant receptors (ORs) and their corresponding arrestins are more likely to be specific for host seeking behaviors in this vector rather than downstream, and therefore more generalized, components of the signal transduction cascade. In preliminary studies, alternative approaches have been undertaken to generate olfactory-enriched cDNA pools derived from female mosquitoes yielding clones for several classes of cDNA with possible olfactory roles including putative OBPs and arrestins from An. gambiae s.s. This proposal seeks to extend these molecular screens with a detailed characterization of the development, spatial and temporal expression patterns of these cDNAs and their protein products within the mosquito's olfactory apparatus. In addition, a biochemical characterization of olfactory arrestins with a particular emphasis on a functional assay to identify protein-protein interactions with potential targets including ORs is proposed. To further refine this analysis, comparative screens will be undertaken between An. gambiae s.s. and it's zoophilic non-vector sibling An. quadriannulatus to identify and characterize peripheral olfactory genes, which are specifically associated with anthropophily and/or zoophily.